1. Field of the Invention
The present invention relates to a novel pharmaceutical composition for total or supplemental parenteral nutrition of patients in need thereof for treatment of shock and other trauma.
More particularly, the present invention relates to a novel composition for use in total or supplemental intravenous nutrition of patients in need thereof, such composition comprising a therapeutically effective amount of triglycerides. The present invention also relates to a therapeutical method of increasing the efficiency of triglyceride administration to patients in need thereof because of their condition of shock and trauma.
2. Description of the Prior Art
Up until recently, total parenteral nutrition was limited to the use of carbohydrates and protein hydrolysates, whereas intravenous administration of fats as caloric source was actually avoided in spite of its acknowledged utility based on the long-standing knowledge that several tissues, particularly the muscular tissue and the myocardium, utilize fatty acids as preferential energy substrate. Consequently, intravenous administration of exogenous fats would result in markedly beneficial effects in all those clinical situations wherein unbalanced conditions of some metabolic systems may occur.
One of these systems is for instance the adjustment system of the lipolysis whose role is that of furnishing suitable material to the tissues which utilize fatty acids and ketone bodies as energy source.
A second system, more closely related to the phenomena of the mitochondrial respiration, is the system wherein the carnitine-acetyl carnitine transferase complex plays an essential role. This complex is strictly related to the activity of ATP mitochondrial translocase and acts so as to allow the passage of the activated, long-chain free fatty acids through the mitochondrial membrane to take place and their attendant conveyance to the beta-oxidation sites.
The consequence brought about by the alterations of the abovementioned systems is the intracellular accumulation of long-chain fatty acids which, therefore, cannot be properly utilized. The muscular cells are thus deprived of an energy substrate of the utmost importance and muscular proteolysis is thereby enhanced with attendant loss of branched-chain aminoacids which are utilized by the muscular tissues for energy purposes. This impaired free fatty acid utilization causes the blockage of several enzyme systems of the mitochondrial walls and the onset of cardiac rhythm disturbances.
More recently, administration of triglycerides to patients affected by conditions of shock and trauma has become a problem of major concern and after extensive experimentation and researches lipid packs in the form of an intravenous emulsion of fats and oils have been developed and become commercially available. As an instance of useful lipid pack, Intralipid (marketed by Cutter Laboratoires, Berkeley, Calif.) can be cited. Intralipid is made up of 10% soybean oil (a mixture of the glycerides of oleic, linolic, palmitic, stearic and linolenic acids), 1.2 egg yolk phospholipids, 2.25% glycerin, the balance being water for injection, sufficient sodium hydroxide being added to adjust the pH to 5.5-9.0.
Other compositions of lipid packs at present available on the market are disclosed in "Total parenteral nutrition" by Parshotam L. Madan, Devendra K. Madan and Joseph F. Palumbo, Drug Intelligence and Clinical Pharmacy, Vol 10, Dec. 76, pages 684-696, and in "L'alimentation parenterale par emulsions lipidiques" by G. Duchesne, La Revue du Praticien (1974), 24, 5, pages 377-384. The disclosures of these articles are incorporated by reference in this specification.
Exogenous triglycerides of the intravenous fat emulsion are intended to be hydrolyzed in the body by lipase with attendant formation of glycerol and fatty acids. These latter should in turn undergo progressive oxidation.